TY - JOUR
T1 - p53 attenuates AKT signaling by modulating membrane phospholipid composition
AU - Rueda-Rincon, Natalia
AU - Bloch, Katarzyna
AU - Derua, Rita
AU - Vyas, Rajesh
AU - Harms, Amy
AU - Hankemeier, Thomas
AU - Khan, Niamat Ali
AU - Dehairs, Jonas
AU - Bagadi, Muralidhararao
AU - Binda, Maria Mercedes
AU - Waelkens, Etienne
AU - Marine, Jean Christophe
AU - Swinnen, Johannes V.
PY - 2015
Y1 - 2015
N2 - The p53 tumor suppressor is the central component of a complex network of signaling pathways that protect organisms against the propagation of cells carrying oncogenic mutations. Here we report a previously unrecognized role of p53 in membrane phospholipids composition. By repressing the expression of stearoyl-CoA desaturase 1, SCD, the enzyme that converts saturated to mono-unsaturated fatty acids, p53 causes a shift in the content of phospholipids with mono-unsaturated acyl chains towards more saturated phospholipid species, particularly of the phosphatidylinositol headgroup class. This shift affects levels of phosphatidylinositol phosphates, attenuates the oncogenic AKT pathway, and contributes to the p53- mediated control of cell survival. These findings expand the p53 network to phospholipid metabolism and uncover a new molecular pathway connecting p53 to AKT signaling.
AB - The p53 tumor suppressor is the central component of a complex network of signaling pathways that protect organisms against the propagation of cells carrying oncogenic mutations. Here we report a previously unrecognized role of p53 in membrane phospholipids composition. By repressing the expression of stearoyl-CoA desaturase 1, SCD, the enzyme that converts saturated to mono-unsaturated fatty acids, p53 causes a shift in the content of phospholipids with mono-unsaturated acyl chains towards more saturated phospholipid species, particularly of the phosphatidylinositol headgroup class. This shift affects levels of phosphatidylinositol phosphates, attenuates the oncogenic AKT pathway, and contributes to the p53- mediated control of cell survival. These findings expand the p53 network to phospholipid metabolism and uncover a new molecular pathway connecting p53 to AKT signaling.
KW - Cancer
KW - Phospholipids
KW - SCD
KW - SREBP
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=84940773140&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940773140&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.4067
DO - 10.18632/oncotarget.4067
M3 - Article
C2 - 26061814
AN - SCOPUS:84940773140
SN - 1949-2553
VL - 6
SP - 21240
EP - 21254
JO - Oncotarget
JF - Oncotarget
IS - 25
ER -
